Effects of Enzymatic Digestion and Probiotic on Oleuropein Bioavailability

• Sponsor: Nestlé (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04328571
• Collaborator: (none)
• Enrollment: 104
• Location: 1
• Arms: 3
• Actual Duration (Months): 19.2
• Patients Per Site Per Month: 5.4

Study Details

Study Description

Brief Summary

This is a 3-arms randomized-controlled, parallel group, single center, double-blind study investigating the bioavailability of olive oil extract (OLE) in two different OLE formulations (enzymatically treated and co-administered with a probiotic) compared to original OLE formulation in healthy adult subjects.

Condition or Disease	Intervention/Treatment	Phase
Healthy Subjects	Dietary Supplement: OLE enzymatically treated; Dietary Supplement: OLE + probiotic; Dietary Supplement: OLE	N/A

Detailed Description

Male or female healthy adults between 25 and 65 years of age will be randomized into one of the 3 following groups to receive:

1. Capsule of OLE + 1 stick of maltodextrin

2. Capsule of OLE enzymatically treated + 1 stick of maltodextrin

3. Capsule OLE + 1 stick of probiotic

52 subjects will be randomized to achieve 15 subjects per group to complete the trial.

The study will involve 3 phases:

1. PK1 (all subjects will receive one capsule of OLE in the morning and blood samples will be collected at different timepoints for 24h) followed by a washout period of 1 day

2. 3 weeks intervention (subjects will receive the product thy have benn assigned to) followed by a wash-out period of 3 days

3. PK2 period (subjects will receive one capsule the product thy have benn assigned to

Study Design

• Study Type: Interventional
• Actual Enrollment: 104 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: 3-arms randomized-controlled, parallel group, single center, double-blinded study investigating 3 different formulations of the investigational product3-arms randomized-controlled, parallel group, single center, double-blinded study investigating 3 different formulations of the investigational product
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: Single coding
• Primary Purpose: Basic Science
• Official Title: Effects of Enzymatic Digestion and Probiotic on Oleuropein Bioavailability
• Actual Study Start Date: Feb 10, 2020
• Actual Primary Completion Date: May 15, 2021
• Actual Study Completion Date: Sep 15, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: OLE enzymatically treated Participants will receive 1 capsule of OLE enzymatically treated + 1 stick of maltodextrin each day in the morning for 21 days	Dietary Supplement: OLE enzymatically treated; OLE (Olive leaf extract ) enzymatically treated + maltodextrin
Experimental: OLE + probiotic Participants will receive 1 capsule of OLE + 1 stick of probiotic each day in the morning for 21 days	Dietary Supplement: OLE + probiotic; OLE (Olive leaf extract) co-administered with probiotic
Active Comparator: OLE Participants will receive 1 capsule of OLE + 1 stick of maltodextrin each day in the morning for 21 days	Dietary Supplement: OLE; OLE (Olive leaf extract) + maltodextrin

Outcome Measures

Primary Outcome Measures

1. AUC0-24h of individual blood oleuropein metabolites during PK2 period [24 hours]

   AUC0-24h (concentration/time curve) of individual blood oleuropein metabolites during PK2 period

Secondary Outcome Measures

1. Cmax during PK2 period [24 hours]

   Cmax of total and individual oleuropein metabolites during PK2 period

2. Tmax during PK2 period [24 hours]

   Tmax of total and individual oleuropein metabolites during PK2 period

3. T1/2 during PK2 period [24 hours]

   T1/2 of total and individual oleuropein metabolites during PK2 period

4. Levels of total and individual oleuropein metabolites in urine at PK2 [24 hours]

   Levels of total and individual oleuropein metabolites excreted in the urine collected over 24 hours during PK2

5. AUC0-24h during PK1 [24 hours]

   AUC0-24h (concentration/time curve) of individual blood oleuropein metabolites during PK1 period

6. Cmax during PK1 [24 hours]

   Cmax of total and individual blood oleuropein metabolites during PK1 period

7. Tmax during PK1 [24 hours]

   Tmax of total and individual blood oleuropein metabolites during PK1 period

8. T1/2 during PK1 [24 hours]

   T1/2 of total and individual blood oleuropein metabolites during PK1 period

9. Levels of total and individual oleuropein metabolites in urine at PK1 [24 hours]

   Levels of total and individual oleuropein metabolites excreted in the urine collected over 24 hours during PK1

10. Change in gut microbiota bacterial population diversity [3 weeks]

    Change from baseline to end of the 3-week intervention period of gut microbiota bacterial population diversity (16SrDNA sequencing)

11. Change in levels of faecal oleuropein metabolites [3 weeks]

    Change from baseline to end of the 3-week intervention period of faecal oleuropein metabolites

Other Outcome Measures

1. Change of gut microbiota faecal short chain fatty acids [3 weeks]

   Change from baseline to end of the 3-week intervention period of gut microbiota faecal short chain fatty acids (acetate, propionate, butyrate) & lactate

2. Change of gut microbiota faecal branched chain fatty acids [3 weeks]

   Change from baseline to end of the 3-week intervention period of gut microbiota faecal branched chain fatty acids (isobutyrate, isovalerate & isocaproate)

3. Change of gut microbiota faecal ammonium production [3 weeks]

   Change from baseline to end of the 3-week intervention period of gut microbiota faecal ammonium production

4. Blood levels of total cholesterol [3 weeks]

   Change from baseline to the end of the 3-week intervention period of total cholesterol levels

5. Blood levels of LDL [3 weeks]

   Change from baseline to the end of the 3-week intervention period of LDL levels

6. Blood levels of HDL [3 weeks]

   Change from baseline to the end of the 3-week intervention period of HDL levels

7. Blood levels of ALAT [3 weeks]

   Change from baseline to the end of the 3-week intervention period of ALAT levels

8. Blood levels of ASAT [3 weeks]

   Change from baseline to the end of the 3-week intervention period of ASAT levels

9. Blood levels of creatinine [3 weeks]

   Change from baseline to the end of the 3-week intervention period of creatinine levels

10. Blood levels of glucose [3 weeks]

    Change from baseline to the end of the 3-week intervention period of glucose levels

11. Blood levels of triglycerides [3 weeks]

    Change from baseline to the end of the 3-week intervention period of triglycerides levels

12. Blood levels of bone biomarkers [3 weeks]

    Change from baseline to the end of the 3-week intervention period of bone biomarkers (P1NP, CTX)

13. Blood levels of Oxidized LDL [3 weeks]

    Change from baseline to the end of the 3-week intervention period of Oxidized LDL

14. Levels of biomarkers of oxidative stress [3 weeks]

    8-NO2GU, 8-OH-GU, 8-OH GUO, 8-OH-DGUO, 8 NO2 GUO, cGMP, 8-NO2-cGMP, Prostanoids, Oxylipins, Isoprostanes, Phytoprostanes and Phytofuranes

Eligibility Criteria

Criteria

• Ages Eligible for Study: 25 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Willing and able to sign written informed consent prior to trial entry

2. Male or female healthy adults between 25 and 65 years of age

3. Body Mass Index (BMI) within the range 18.5 - 29.9 (both inclusive)

4. In good health as determined by medical judgment and medical history

Exclusion Criteria:

1. Any food allergy/intolerance

2. Subjects not willing and/or not able to comply with scheduled visits and the requirements of the study protocol

3. Taking or anticipated initiation of any lipid-modifying or blood-clotting medication e.g. statins, cholesterol lowering

4. Smokers

5. Alcohol intake higher than 2 servings per day (one serving is 0.4 dL of strong alcohol, 1 dL of wine, or 3 dL of beer) or drug abuse

6. Receiving or having received antibiotics in the past 4 weeks prior to the day of inclusion

7. Overly imbalanced or restrictive diet (e.g. hyperproteic, vegan, ketogenic, etc.)

8. Hormonal treatment for women linked to menopause (contraceptive treatment accepted)

9. Pregnancy or breastfeeding

10. Supplements or foods containing probiotics (yogurts allowed)

11. Currently participating or having participated in another clinical trial within 4 weeks prior to trial start

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Universidad Católica San Antonio	Murcia		Spain	30107

Sponsors and Collaborators

• Nestlé

Investigators

• Principal Investigator: Francisco A. Tomás-Barberán, Prof., CEBAS-CSIC, Murcia, Spain

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Nestlé
• ClinicalTrials.gov Identifier: NCT04328571
• Other Study ID Numbers: 1907NRC
• First Posted: Mar 31, 2020
• Last Update Posted: Oct 1, 2021
• Last Verified: Sep 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Study Results

No Results Posted as of Oct 1, 2021